Strengthening intersubunit hydrogen bonds for enhanced stability of recombinant urate oxidase from Aspergillus flavus: molecular simulations and experimental validation | |
Liu, Zhixia ; Lu, Diannan ; Li, Jianmin ; Chen, Wei ; Liu, Zheng | |
2010-10-12 ; 2010-10-12 | |
关键词 | ESCHERICHIA-COLI HYPERURICEMIA EXPRESSION THERMOSTABILITY DEHYDROGENASE MANAGEMENT RESOLUTION LYMPHOMA URICASE SUBUNIT Chemistry, Physical Physics, Atomic, Molecular & Chemical |
中文摘要 | The aim of this study was to obtain molecular insight into the deactivation of recombinant urate oxidase (uricase, UOX, EC 1.7.3.3) (rUOX) from Aspergillus flavus. The enzyme is a tunnel-shaped homotetramer and has important clinical applications. By means of molecular dynamics simulations, multidimensional structural characterization and enzyme activity assays, we concluded that the thermal deactivation of UOX at neutral pH was associated with the loss of intersubunit hydrogen (H) bonds. This mechanism could also explain the deactivation of dilute aqueous UOX. Thermal deactivation of aqueous UOX due to dissociation of its subunits was ruled out. Displacement of H2O from the surface of UOX by less polar solvents such as methanol and dimethyl sulfoxide (DMSO) was proposed as an approach for strengthening intersubunit H bonds and consequently UOX stability. The effectiveness of this method was validated by both in silico and in vitro experiments. The results mentioned above provide insights for improving the stability of UOX and extending its applications. They may also be helpful for understanding the properties of other multimeric proteins. |
语种 | 英语 ; 英语 |
出版者 | ROYAL SOC CHEMISTRY ; CAMBRIDGE ; THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND |
内容类型 | 期刊论文 |
源URL | [http://hdl.handle.net/123456789/79613] |
专题 | 清华大学 |
推荐引用方式 GB/T 7714 | Liu, Zhixia,Lu, Diannan,Li, Jianmin,et al. Strengthening intersubunit hydrogen bonds for enhanced stability of recombinant urate oxidase from Aspergillus flavus: molecular simulations and experimental validation[J],2010, 2010. |
APA | Liu, Zhixia,Lu, Diannan,Li, Jianmin,Chen, Wei,&Liu, Zheng.(2010).Strengthening intersubunit hydrogen bonds for enhanced stability of recombinant urate oxidase from Aspergillus flavus: molecular simulations and experimental validation.. |
MLA | Liu, Zhixia,et al."Strengthening intersubunit hydrogen bonds for enhanced stability of recombinant urate oxidase from Aspergillus flavus: molecular simulations and experimental validation".(2010). |
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